Fluorescent sensors and probes have attracted attention because of their high sensitivity and exceptional ease of handling relative to their radioactive counterparts. Combinatorial chemistry is now widely used in the medicinal/pharmaceutical field and in chemical biology for the discovery of new biologically active molecules or drug candidates. The application of this method to fluorescent dyes is still quite new. A few early examples include oligopyridines, coumarins, oligonucleotides, and conjugated polymers. Application Ser. No. 10/656,875 discloses the first combinatorial wide-color-range fluorescent styryl library by solution-phase chemistry and their potential application as organelle-specific probes. Application Ser. No. 11/104,451 discloses another group of compounds that can be used as fluorescent dyes.
Unfortunately, it has been discovered that positively charged compounds cannot stain brain tissue to identify misfolded proteins.
Amyloids represent a case of protein misfolding leading to the formation of ordered secondary structures rich in cross β-sheets, which are present as fibrillar deposits in tissues.6 Amyloid formation had been associated with a large number of protein misfolding diseases including type II diabetes, Alzheimer's, Parkinson's, Huntington's, mad-cow disease, and others.7,8 Among the many amyloidoses, Alzheimer's disease (AD) is the fourth leading cause of death in the United States, and the most common cause of adult-onset dementia.9,10 The deposition of β-amyloid (Aβ) aggregates in brain tissue is one of the hallmark characteristics in AD and the efficient imaging agents of amyloid plaque for the diagnosis of AD would be particularly helpful in diagnosing this disease while the patient is still alive.11 